炎琥宁对脂多糖诱导急性肺损伤的防治作用及机制OA

Objective To establish a murine model of acute lung injury(ALI)via intratracheal instillation of lipopolysaccharide(LPS)and investigate the therapeutic/preventive effects and underlying mechanism of Yanhuning for Injection on ALI.Methods The mice were randomly divided into six groups,following drug administration and modeling,bronchoalveolar lavage fluid(BALF)and lung tissue specimens were collected from each group.Six inflammatory markers,including IL-1β,IL-6 and TNF-α,etc,were measured in the BALF.Histopathological sections were scored for inflammation.The content of MDA and the activity of SOD in the tissues were measured.RT-qPCR was used to detect the mRNA expression levels of TLR4,NLRP3,NF-κB p65,JNK,Erk1/2 and p38.Western blotting was employed to determine the protein expression levels of NLRP3,TLR4,NF-κB p65,JNK,Erk1/2 and p38.Results Compared to the LPS model group,Yanhuning for Injection ameliorated lung tissue damage,reduced histopathological inflammation scores,and attenuated the inflammatory response in the ALI mouse model.It significantly increased the SOD activity and decreased the MDA content in the model group.It also significantly reduced the total cell count,total protein concentration,and the levels of inflammatory cytokines IL-1β,IL-6 and TNF-α in the model group.The expression levels of TLR4,NLRP3,NF-κB p65,JNK,Erk1/2,p38 proteins,and their corresponding mRNAs were markedly downregulated.Conclusion Yanhuning can significantly alleviate the degree of lung injury in LPS-induced ALI mice,inhibit pulmonary inflammatory responses,reduce oxidative damage,and enhance antioxidant capacity.The mechanism of Yanhuning's preventive effects on ALI is related to the inhibition the activation of TLR4/NF-κB and MAPK signaling pathway.